Elsevier

The Lancet

Volume 360, Issue 9332, 17 August 2002, Pages 516-520
The Lancet

Articles
Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia

https://doi.org/10.1016/S0140-6736(02)09740-4Get rights and content

Summary

Background

Despite the introduction of the parenteral iron chelator desferrioxamine more than 30 years ago, 50% of patients with thalassaemia major die before the age of 35 years, predominantly from iron-induced heart failure. The only alternative treatment is oral deferiprone, but its longterm efficacy on myocardial iron concentrations is unknown.

Methods

We compared myocardial iron content and cardiac function in 15 patients receiving long-term deferiprone treatment with 30 matched thalassaemia major controls who were on long-term treatment with desferrioxamine. Myocardial iron concentrations were measured by a new magnetic-resonance T2* technique, which shows values inversely related to tissue iron concentration.

Findings

The deferiprone group had significantly less myocardial iron (median 34·0 ms vs 11·4 ms, p=0·02) and higher ejection fractions (mean 70% [SD 6·5] vs 63% [6·9], p=0·004) than the desferrioxamine controls. Excess myocardial iron (T2* <20 ms) was less common in the deferiprone group than in the desferrioxamine controls (four [27%] vs 20 [67%], p=0·025), as was severe (T2* <10 ms) iron overload (one [7%] vs 11 [37%], p=0·04). The odds ratio for excess myocardial iron in the desferrioxamine controls versus the deferiprone group was 5·5 (95% CI 1·2–28·8).

Interpretation

Conventional chelation treatment with subcutaneous desferrioxamine does not prevent excess cardiac iron deposition in two-thirds of patients with thalassaemia major, placing them at risk of heart failure and its complications. Oral deferiprone is more effective than desferrioxamine in removal of myocardial iron.

Introduction

Heart failure due to iron overload can develop either as a result of excess dietary absorption (hereditary haemochromatosis) or from repeated blood transfusions. The most striking model of cardiac iron overload is seen in thalassaemia major, in which heart failure remains the major cause of death (60%), greatly exceeding deaths from infection (13%) and liver disease (6%).1 Despite the introduction of the iron-chelating agent desferrioxamine more than 30 years ago in the UK, 50% of patients still die before reaching the age of 35 years.2 This high mortality is partly the result of difficulties with administration of desferrioxamine. This drug requires long subcutaneous or intravenous infusions on at least 4 days a week; compliance with treatment is inadequate in many cases. The need for an effective alternative approach with an oral iron chelator has long been acknowledged,3 and medium-term results from prospective trials of the oral chelator deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one) seemed promising;4, 5, 6 however, the long-term effectiveness of this drug has been questioned because liver iron content is high in some patients.7, 8 Since the primary objective of iron-chelation therapy is to prevent the lethal cardiac complications from myocardial iron deposition, myocardial iron and ventricular function should also be taken into account in assessment of the effectiveness of chelating agents. New magnetic resonance techniques can assess both myocardial iron and ventricular function in the same study.9 Our aim, therefore, was to investigate whether deferiprone is effective in controlling myocardial iron.

Section snippets

Participants

We included all patients based at the Whittington Hospital, London, UK, who received chelation with deferiprone alone for longer than 3 years (mean duration 5·7 years [SD 1·8]), between May, 1999, and December, 2000. For each deferiprone patient, we assigned two controls with thalassaemia major, matched for age, sex, and current ferritin concentration, who were receiving standard subcutaneous desferrioxamine. Controls were chosen from the thalassaemic population also treated at this centre. The

Results

Clinically relevant characteristics for patients in the two study groups are compared in table 1.

The deferiprone-treated group had significantly less myocardial iron than the desferrioxamine-treated group (median myocardial T2* 34·0 vs 11·4 ms, p=0·02, table 2). The deferiprone group also had a higher mean left-ventricular ejection fraction (p=0·004) and less left-ventricular dilatation in systole (p=0·03) and diastole (p=0·01) than the control group. The left-ventricular mass index was lower,

Discussion

The iron chelator desferrioxamine was introduced more than 30 years ago13, 14 and remains the only chelator approved for regular use in North America and the only first-line agent approved for use in Europe. Desferrioxamine improves hepatic, cardiac, and endocrine dysfunction and lengthens survival in patients with iron overload.15, 16, 17 The disadvantages include high cost,18 the requirement for daily parenteral administration, and local and systemic toxic effects, which include visual19 and

References (30)

  • NF Olivieri et al.

    Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major

    N Engl J Med

    (1998)
  • LJ Anderson et al.

    Cardiovascular T2* magnetic resonance for the early diagnosis of myocardial iron overload

    Eur Heart J

    (2001)
  • NG Bellenger et al.

    Establishment and performance of a magnetic resonance cardiac function clinic

    J Cardiovasc Magn Reson

    (2000)
  • NG Bellenger et al.

    Reduction in sample size for studies of remodelling in heart failure by the use of cardiovascular magnetic resonance

    J Cardiovasc Magn Reson

    (2000)
  • CH Lorenz et al.

    Normal human right and left ventricular mass, systolic function and gender differences by cine magnetic resonance imaging

    J Cardiovasc Magn Reson

    (1999)
  • Cited by (0)

    View full text